Genetic Diversity of the Pneumococcal Capsule: Implications for Molecular-based Serotyping

Mary Catherine McEllistrem

Disclosures

Future Microbiol. 2009;4(7):857-865. 

In This Article

Abstract and Introduction

Abstract

Streptococcus pneumoniae remains an important pathogen despite licensure of a seven-valent pneumococcal protein conjugate vaccine. As a result, serotyping strains remains of paramount importance to both assess the effectiveness of current vaccines and closely monitor for the emergence of nonvaccine strains. Given the limitations of the quellung reaction, both molecularand immunology-based serotyping methods have been pursued. Currently, the most promising assay combines an immunologic assay with multiplex PCR of serotype-specific genes. The key limitation with a molecular-based assay is the plasticity of the pneumococcus, as capsular transformation or point mutations could easily result in serotype misclassification. Based on the currently available techniques, a comprehensive immunology-based assay appears to be the most promising alternative to the quellung reaction. In the future, assays that utilize high-throughput sequencing technology and/or matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI–TOF MS) could lead to a novel pneumococcal serotyping method.

Introduction

In addition to being a prominent cause of invasive disease, Streptococcus pneumoniae is the most common bacterial cause of otitis and community-acquired pneumonia. The 23-valent pneumococcal polysaccharide vaccine (PPV23) provides protection against invasive disease due to 23 of the 91 serotypes in high-risk persons, and includes serotypes 1–5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F. A seven-valent pneumococcal protein conjugate vaccine (PCV7), consisting of serotypes 4, 6B, 9V, 14, 18C, 19F and 23F, was licensed in 2000 and is now routinely given to infants and children. The incidence of invasive pneumococcal disease has significantly declined in the USA due to the receipt of PCV7 in children and herd immunity in adults.[1] However, serotype replacement with strains not included in PCV7 has occurred at a rapid rate in some populations.[2–5] Among native Alaskan children, the incidence of invasive pneumococcal disease caused by non-PCV7 serotypes increased from 95.1 to 228.6/100,000 between 1995–2000 and 2004–2006,[5] demonstrating that serotype replacement disease can erode the efficacy of PCV7. Likewise, the incidence of non-PCV7 serotype 19A in the USA significantly increased between 1998 and 2005.[6] A 13-valent pneumococcal conjugate vaccine (PCV13) will likely be licensed for infants and young children in the near future. This vaccine includes the PCV7 serotypes plus serotypes 1, 3, 5, 6A, 7F and 19A. While this vaccine could potentially further decrease invasive disease, concerns over additional serotype replacement still abound. As a result, serotyping strains remains of paramount importance to both assess the effectiveness of current vaccines and closely monitor for the emergence of nonvaccine strains.

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